1. Technical Field
The embodiments herein generally relate to the field of molecular imaging and particularly to multimodal molecular imaging. The embodiments herein more particularly relate to gold coated super paramagnetic iron oxide nano-particles. The embodiments herein also relate to a method of synthesizing the gold coated super paramagnetic iron oxide nano-particles with a jagged surface.
2. Description of the Related Art
With the entry of nanoscience in the medical field, one can hope for early diagnosis together with the prompt treatment of catastrophic diseases like (e.g. cancer). The treatment of these catastrophic diseases has been dramatically increased with the entrance of nanoscience. Development of multifunctional engineered nanoparticles (NPs) with desired physiochemical properties, as nano-probes, has enabled new imaging modalities which have great capability in molecular imaging and medical theragnosis and which are essential for early detection and rapid treatment of diseases. It is noteworthy to mention that these multimodalities of engineered NPs are beyond the observed intrinsic properties of individual NPs comprising materials. In the recent few decades, nanoparticles (NPs) have been recognized as promising candidates for the creation of new revolution in science and technology due to their unusual properties which have attracted the attention of physicists, chemists, biologists and engineers. The appearance of NPs in medical sciences either introduced new opportunities or caused significant enhancements in the conventional biomedical methods (e.g. imaging purposes). The creation of novel engineered multimodal NPs is a key focus in bio-nanotechnology and can lead to advancement in the deep understanding of the biological processes at the biomolecular level thereby causing the great impact on molecular diagnostics, imaging and therapeutic applications.
Ever since the medical diagnosis era was initiated by Wilhelm Roentgen, who captured the first X-ray image of his wife's hand in 1896, X-rays have been extensively employed in the medical imaging of anatomical details. However, cellular and molecular imaging still remained as dreams in medical field. With the development of nano science, this dream is coming true. The advantage of using multimodal NPs, in comparison with individual NPs (e.g. semiconductor quantum dots, magnetic and metallic NPs), for cellular or biomolecular tracking, is the capability of multimodal NPs to provide a high spatial resolution with high anatomic background contrast, together with the lack of exposure to ionizing radiation and the ability to follow the cells for months.
During the last decade, various approaches using different imaging techniques as well as various contrast agents have been employed to enhance the efficacy of biomolecular imaging. Among the various NPs employed in the biomolecular imaging methods, the super paramagnetic iron oxide nano particles (SPIONs) have been recognized as one of the most important nano-probes because of their multi-modality and multi-tasking property. Various methods have been employed for producing these SPIONs. One of the methods involves employing a polyol route. Briefly, 5 mL of an aqueous solution of FeCl2.4H2O (0.045 mol) and FeCl3 (0.0375 mol) were added to 250 mL of diethylene glycol. The mixture was heated to 170° C. and maintained at this temperature for 15 min before addition of the base (i.e. solid NaOH (0.375 mol)). Afterward, the temperature was maintained at 170° C. for a period of 1 h before cooling at 60° C. The synthesized SPIONs were collected with neodymium magnet and washed with 100 mL of a HNO3 1N solution. The SPIONs have excellent biocompatibility.
Individual NPs, as nanoprobes, present their distinct advantages and limitations. In this case, super paramagnetic iron oxide NPs (SPIONs) are recognized as suitable contrast agent in T2-weighted magnetic resonance imaging (MRI). However, SPIONs are not sensitive in optical imaging or positron emission tomography. In order to make them sensible to other imaging modes (e.g. optical imaging), their surfaces or structures should be modified. For examples, radioactive-doped SPIONs could be traced with positron emission tomography and gamma spectroscopy imaging methods.
Gold NPs with their unique optical and melting properties were introduced in 1996 by an aggregation of gold NPs (at a diameter of 13 nm) and oligonucleotides. The above mentioned aggregate scattering properties together with the interaction between particle surface plasmons as the distance between NPs resulted in a variation in the color of gold NPs. This distance-dependent optical property has led to the use of gold NPs in a plethora of biomolecular detection methods, starting with colorimetric systems. More specifically, the gold NP bioconjugates were employed for the detection of polynucleotide using the change in optical properties resulting from plasmon-plasmon interactions between locally adjacent gold NPs. Due to their colorimetric contrast which is induced by surface plasmon resonance, the gold NPs can be used as contrast agents in biomolecular imaging. The main problem with individual gold NPs for in vivo imaging applications is their low tissue penetration depth which is limited to millimeters. Therefore, a major challenge is how to engineer or enhance molecular probes with integrated functionalities while still maintaining the compact sizes. In addition, it is highly attractive to have multi-task-nano probes with several functionalities which enable new imaging modes, not available from each individual component for enhanced contrast specificity. Several reports disclose the works on the creation of multimodal coupled NPs to achieve better molecular imaging, for instance Loo et al. employed a novel class of contrast agents based on nanoshell (i.e. composition of a dielectric silica core covered by a thin gold shell) bioconjugates for biomolecular imaging. The authors claimed that nanoshells have a great potential to offer advantages over conventional imaging probes, such as continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. According to their results, the prepared nanoshell bioconjugates could be used for targeting and imaging of human epidermal growth factor receptor 2 (i.e. HER2) in live human breast carcinoma cells. The same group employed these nanoshells for dual imaging or therapy to detect and destroy breast carcinoma cells that over-express HER2. It has been shown that gold high-density lipoprotein NPs, as contrast agents, can significantly improve CT imaging for characterization of macrophage burden, calcification, and stenosis of atherosclerotic plaques.
The combination of gold and magnetic NPs (i.e. gold coating on the surface of magnetic NPs) with controllable shell thickness and smooth surface can be used for multi-task applications including contrast enhancing in MRI, magnetic attraction, near-infrared absorption (NIR), and photon scattering applications. Lyon et al. reported a formation of stable magnetic core-shell NPs in aqueous media through rapid and effective route. The several reports are dedicated to the creation of direct gold coating on the surface of SPIONs. None of the approach simultaneously produces NPs with NIR response and also the obtained materials are critical for in vivo imaging and therapy, and maintains compact particle size, which affects tissue penetration and plasma circulation. Jin et al. reported a new generation of compact, uniform, NIR responsive gold coated SPIONs by creating a gap between the core and the shell. The smooth gold-shell SPIONs were prepared according to the previous report. Briefly, the prepared SPIONs were mixed with PL-PEG-COOH (ratio of 1:1.5 W/W) in chloroform and remained, till the solvent were evaporated slowly. The residual coated SPIONs were heated to 80° C. for 5 min and re-dispersed in DI water with sonication. The obtained materials were collected with strong magnet and washed several times with DI water. PLH was added to the solution of SPIONs and the pH was adjusted among 5-6, using 0.1 N HCl. After incubation for 60 min, the magnetic NPs were collected with magnet and washed several times with DI water. The obtained solution was mixed with HAuCl4 (w/w 1%), for 20 min where the pH was adjusted among 9-10 with NaOH. Afterward, NH2OH. HCL was added to the solution and mixed well till the colour of colloidal suspension turned to dark blue. It is noteworthy that the observed colour was cleared in a few minutes. The achieved solution was washed several times, re-dispersed in DI water using sonicator, and kept between 2-8° C. In this case, a magnetically sensitive NP with strong NIR and MRI responses together with magnetomotive photoacoustic (mmPA) imaging capability were obtained. But the responses obtained were not of the desired expectations and also there was no effect on Surface Enhanced Raman Spectroscopy (SERS).
Hence there is a need to engineer a new generation of compact and uniform gold coated SPIONs by creating a non-uniform gap between the core and the shell with enhanced imaging properties and Surface Enhanced Raman Spectroscopic (SERS) properties.
The above mentioned shortcomings, disadvantages and problems are addressed herein and which will be understood by reading and studying the following specification.